Medical assembly suitable for long-term implantation and method for fabricating the same

ABSTRACT

A process for fabricating a medical assembly having a medical device at least a portion of which is formed of inorganic material is provided. The medical assembly is suitable for substantially long-term implantation in a host animal. The process includes modifying a surface of the medical device to form a hydrophilic adhesion-promoting surface. The hydrophilic adhesion-promoting surface is coated with an alginate solution comprising alginate and the alginate is reacted with alkaline earth metal cations.

FIELD OF THE INVENTION

This invention relates generally to implantable medical devices and morespecifically to medical devices coated with alginate material forlong-term implantation into living tissue of a host and methods ofmaking the same.

BACKGROUND OF THE INVENTION

Medical treatments for the shortcomings or functional deficiencies ofbiological organs and systems have long included the implantation ofinorganic medical devices or the implantation of medical devices thatare formed, at least in part, of inorganic materials. Such medicaldevices are designed to restore or replace a useful biological functionneeded by the host animal. Implantable medical devices have beendesigned to perform a variety of biological functions, including,without limitation, restoring the functioning of a failed heart,monitoring the chemical or electrical stimuli produced by a system ororgan, secreting needed synthetic pharmaceutical compositions, anddraining undesirable fluids from organs or tissues. Implantable devicessuch as catheters, stents, fluid flow control valves, biosensors,pressure sensors, pacemakers and the like are well known in the medicalindustry.

The implantation of such device for long periods of time, that is, onthe order of months or years, has often proven unsuccessful due torejection by the immunological system of the host animal, particularlyas a result of fibrous tissue growth. Fibrous tissue growth can impairthe operation of certain devices such as, for example, sensors. Fibroustissue growth can also reduce the efficiency of devices such aselectrodes in pacing devices and antennas in in-vivo telemetry systems.

Current solutions for the prevention of fibrous tissue growth onimplanted devices have included the use of timed releasable drugs ormolecules, such as heparin or other antibiotics and antithrombogenics.However, such methods typically have proven to be short-term solutions,that is, on the order of days to months. In addition, the use of suchdrugs is costly, may have deleterious effects on the immune system ofthe host animal, and may subject the host animal to the side effects ofthe drugs.

Accordingly, a need exists for a medical device suitable for long-termimplantation in a host animal. A need also exists for a process forfabricating a medical device suitable for long-term implantation in ahost animal.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is illustrated by way of example and notlimitation in the accompanying figures, in which like referencesindicate similar elements, and in which:

FIG. 1. is a cross-sectional view of a medical device coated with abiocompatible material;

FIG. 2 is a cross-sectional view of the medical device of FIG. 1comprising a hydrophilic adhesion-promoting surface;

FIG. 3 is a cross-sectional view of the medical device of FIG. 2 coatedwith an alginate material; and

FIG. 4 is a cross-sectional view of the medical device of FIG. 3 coatedwith a gelled alginate.

Skilled artisans will appreciate that elements in the figures areillustrated for simplicity and clarity and have not necessarily beendrawn to scale. For example, the dimensions of some of the elements inthe figures may be exaggerated relative to other elements to help toimprove understanding of embodiments of the present invention.

SUMMARY OF THE INVENTION

This summary of the invention section is intended to introduce thereader to aspects of the invention and may not be a complete descriptionof the invention. Particular aspects of the invention are pointed out inother sections herein below, and the invention is set forth in theappended claims which alone demarcate its scope.

In accordance with an exemplary embodiment of the present invention, aprocess for fabricating a medical assembly having a medical device, atleast a portion of which is formed of inorganic material, is provided.The medical assembly is suitable for substantially long-termimplantation in a host animal. The process includes modifying a surfaceof the medical device to form a hydrophilic adhesion-promoting surface,coating the hydrophilic adhesion-promoting surface with an alginatesolution comprising alginate, and reacting the alginate with alkalineearth metal cations.

In accordance with another exemplary embodiment, a medical assemblysuitable for substantially long-term implantation in a host animal isprovided. The medical assembly includes a medical device at least aportion of which is formed of inorganic material. The medical assemblyalso includes a hydrophilic adhesion-promoting surface formed on themedical device and a gelled alginate coating overlying the hydrophilicadhesion-promoting surface.

DETAILED DESCRIPTION OF THE INVENTION

The following description is of exemplary embodiments only and is notintended to limit the scope, applicability or configuration of theinvention in any way. Rather, the following description provides aconvenient illustration for implementing exemplary embodiments of theinvention. Various changes to the described embodiments may be made inthe function and arrangement of the elements described without departingfrom the scope of the invention as set forth in the appended claims.

FIGS. 1–4 illustrate a process in accordance with one exemplaryembodiment of the invention for making a medical assembly that issuitable for long-term implantation in a host animal. Referring to FIG.1, a medical device 10 is provided. Medical device 10 may include anymechanism that performs or provides a useful biological function. Atleast a portion of medical device 10 is formed of inorganic material,although it will be appreciated that medical device 10 may also compriseany suitable amount of organic matter. Medical device 10 may include,without limitation, pressure sensors, biosensors, catheters, stents,fluid flow control valves, such as cerebral spinal fluid flow controlvalves, and the like. Medical device 10 may also include any suitablepackaging, material or protected manufacturing environment for in-vivobiological factories.

In accordance with one exemplary embodiment of the invention, a surfaceof medical device 10 may be treated to render the surface more adhesiveto later-applied materials, as described in more detail below. Oneexemplary method for rendering a surface of medical device 10 moreadhesive includes coating medical device 10 with a biocompatible polymercoating 20 that renders the surface of medical device 10 more adhesiveto later-applied materials, as illustrated in FIG. 1. Biocompatiblepolymer coating 20 may also serve to round any sharp, pointed, rough orotherwise problematic areas of medical device 10 that, without suchcoating, would otherwise lead to fibrosis or thrombosis. One example ofmaterial suitable for forming biocompatible polymer coating 20 issilicone, although it will be appreciated that any other suitablepolymer that is biocompatible with the host animal and renders thesurface of medical device 10 more adhesive may be used.

Another exemplary method for rendering a surface of medical device 10more adhesive includes oxidizing medical device 10 or coating medicaldevice 10 with an material which can be oxidized to render it morereadily adhesive to later-applied materials. For example, if medicaldevice 10 is formed on a silicon wafer, such as in the case of certainpressure sensors, medical device 10 may be oxidized to form a silicondioxide layer on its surface. The silicon dioxide surface of medicaldevice 10 permits adhesion of later-applied materials while alsorendering medical device 10 hydrophilic.

It will be appreciated that the entire surface of medical device 10 or,alternatively, only portions or components of the surface of medicaldevice 10 may be treated to enhance adhesiveness. The type and design ofmedical device used, the materials from which the medical device is madeand the desired duration of implantation in the host animal may all befactors that determine the amount and positioning of surface to betreated.

As illustrated in FIG. 2, the surface of medical device 10 then ismodified to form a hydrophilic adhesion-promoting surface 30.Hydrophilic adhesion-promoting surface 30 allows ready adhesion of thesubsequently-applied alginate material, described in more detail below,and provides a biocompatible hydrophilic surface. In one exemplaryembodiment, the surface of medical device 10 may be modified to formhydrophilic adhesion-promoting surface 30 by applying anadhesion-promoting material that promotes adhesion between medicaldevice 10 (and/or biocompatible polymer coating 20) and a later-appliedalginate material, discussed in more detail below. Theadhesion-promoting material may be applied by any suitable method thatpermits controlled, even distribution of the adhesion-promoting materialon medical device 10. For example, the adhesion-promoting material maybe spray-coated onto medical device 10 or may be brush-coated ontomedical device 10. Alternatively, medical device 10 may be suspended orimmersed in the adhesion-promoting material. In a further example, theadhesion-promoting material may be vaporized and permitted to bedeposited on a desired surface of medical device 10. It will beappreciated that any other suitable method for applying theadhesion-promoting material to medical device 10 may be used. It willfurther be appreciated that the adhesion-promoting material maydeposited on all surfaces or, alternatively, on only selected surfacesof medical device 10 as may be suitable for a desired application ormedical device. One example of a material that is suitable for forminghydrophilic adhesion-promoting surface 30 is N,N-diethylaminotrimethylsilane (“DEATS”), available from suppliers suchas MicroSi, Inc. of Phoenix, Ariz. DEATS is a low viscosity organosilanetypically used as a photoresist adhesion promoter. Another example of amaterial that is suitable for forming hydrophilic adhesion-promotingsurface 30 is polyvinyl pyrrolidone (PVP), such as that available fromParchem Trading Ltd. of White Plains, N.Y. It will be appreciated thatany other material suitable for forming a biocompatible hydrophilicadhesion-promoting surface, or any suitable combination or layering ofsuch materials to form a biocompatible hydrophilic adhesion-promotingsurface, may also be used.

In another exemplary embodiment of the invention, the surface of medicaldevice 10 may be modified to form hydrophilic adhesion-promoting surface30 by subjecting biocompatible polymer 20 to plasma bombardment. Plasmabombardment of polymers for enhanced adhesion bonding is well known inthe polymer industry. Plasma bombardment is performed such that at leastthe surface of polymer 20 is altered chemically to provide improvedadhesive properties. In yet another exemplary embodiment of theinvention, medical device 10 may be coated with an additionalbiocompatible polymer, which is subsequently subjected to plasmabombardment. One example of a biocompatible polymer that may besubjected to plasma bombardment to form surface 30 includes, withoutlimitation, polytetraflouroethylene (PTFE).

Referring to FIG. 3, once hydrophilic adhesion-promoting surface 30 hadbeen formed on medical device 10, medical device 10 may be subjected toan alginate solution to coat it with an alginate coating 40. Alginate isobtained from seaweed and is a linear unbranched polymer containing□-(1–4)-linked D-mannuronic acid and {tilde over (□)}(1–4)-linkedL-guluronic acid residues. Changes in the physical properties ofalginate in the presence of various ions are exploited in the exemplaryembodiments of the present invention. In the presence of monovalentcounter ions such as sodium and potassium, alginate solutions areliquid. In the presence of multivalent cations such as calcium, bariumand zinc, the alginate forms a gel. The alginate solution may includeany alginate capable of forming a non-fibrogenic, gelled coating on oraround medical device 10. In a preferred embodiment of the invention,the alginate solution is formed of a low viscosity sodium alginate.

In another exemplary embodiment of the present invention, before medicaldevice 10 is subjected to the alginate solution, the alginate solutionmay be purified to remove particulates, fucose, organic contaminantssuch as polyphenols, and other fibrosis-generating components. Oneexemplary method for purifying sodium alginate is disclosed in U.S. Pat.No. 5,429,821 issued Jul. 4, 1995 to Dorian et al.

The medical device 10 may be subjected to the alginate solution by anymethod that permits the hydrophilic adhesion promoting surface 30 ofmedical device 10 to be coated by the alginate material. It will beappreciated that the alginate material may be deposited to coat entiremedical device 10 or to coat only portions of medical device 10depending on the surfaces of medical device 10 treated to formhydrophilic adhesion-promoting surface 30.

It also will be appreciated that the alginate solution may be applied tothe hydrophilic adhesion promoting surface 30 of medical device 10 byany method suitable for appropriately coating hydrophilic adhesionpromoting surface 30 with alginate material. For example, in oneexemplary embodiment of the present invention, medical device 10 may besuspended in the alginate solution for an appropriate amount of time toallow for suitable coating of medical device 10 by the alginatematerial. In another embodiment of the present invention, medical device10 may be spray-coated with the alginate solution. In yet anotherembodiment of the present invention, the alginate solution may bebrushed or “painted” on medical device 10.

Referring to FIG. 4, medical device 10 then is contacted with a suitablegelling solution to form a gelled alginate coating 50, thereby formingmedical assembly 60. The gelling solution includes alkaline earth metalcations, such as calcium, barium, zinc and the like, that result in thegelling of the alginate material. In one exemplary embodiment of thepresent invention, the gelling solution includes calcium chloride orbarium chloride. In a preferred embodiment of the present invention, thealginate coating is gelled by subjecting medical device 10 first to asolution of calcium chloride and then to a solution of barium chloride.Without being limited by any particular theory, it is believed that inthis preferred embodiment the calcium cross-links with the guluronicacid blocks of the alginate molecules, and the barium cross-links withthe mannuronic block of the alginate molecules and the guluronicportions which have not previously been cross-linked with the calciumchloride.

Medical device 10 may be contacted with the gelling solution by anysuitable method, such as by submerging medical device 10 in the gellingsolution, spray-coating medical device 10 with the gelling solution, andbrush-coating medical device 10 with the gelling solution. It will beappreciated, however, that gelling solution may be applied to medicaldevice 10 by any other method suitable for appropriately gelling thealginate material.

It will now be appreciated that medical assembly 60 of the presentinvention is configured to be implanted into the body of a host animalfor long durations, typically on the order of from hours to years,without the negative effects caused by fibrous tissue growth andimmunological rejection. According to various embodiments of the medicalassembly of the present invention, as described above, the medicalassembly comprises a medical device that is coated or encapsulated in agelled alginate material. The gelled alginate material renders themedical device effectively “bioinvisible,” that is, the medical devicebecomes a substantially systemically, pharmacologically inert substancewith the deleterious effects from fibrosis substantially reduced oreliminated.

In the foregoing specification, the invention has been described withreference to specific embodiments. However, one of ordinary skill in theart appreciates that various modifications and changes can be madewithout departing from the scope of the present invention as set forthin the claims below. Accordingly, the specification and figures are tobe regarded in an illustrative rather than a restrictive sense, and allsuch modifications are intended to be included within the scope ofpresent invention.

Benefits, other advantages, and solutions to problems have beendescribed above with regard to specific embodiments. However, thebenefits, advantages, solutions to problems, and any element(s) that maycause any benefit, advantage, or solution to occur or become morepronounced are not to be construed as a critical, required, or essentialfeatures or elements of any or all the claims. As used herein, the terms“comprises,” “comprising,” or any other variation thereof, are intendedto cover a non-exclusive inclusion, such that a process, method,article, or apparatus that comprises a list of elements does not includeonly those elements but may include other elements not expressly listedor inherent to such process, method, article, or apparatus.

1. A process for fabricating a medical assembly having a medical deviceat least a portion of which is formed of inorganic material, saidmedical assembly suitable for substantially long-term implantation in ahost animal, said process comprising: modifying a surface of the medicaldevice with plasma to form a hydrophilic adhesion-promoting surface;coating said hydrophilic adhesion-promoting surface with an alginatesolution comprising alginate; and reacting the alginate with alkalineearth metal cations.
 2. A process for fabricating a medical assemblyhaving a medical device at least a portion of which is formed ofinorganic material, said medical assembly suitable for substantiallylong-term implantation in a host animal, said process comprising:modifying a surface of the medical device with plasma to form ahydrophilic adhesion-promoting surface; coating said hydrophilicadhesion-promoting surface with an alginate solution comprisingalginate; and reacting the alginate with alkaline earth metal cationswherein coating the medical device with the biocompatible material priorto said modifying.
 3. The process of claim 2, said biocompatiblematerial comprising silicone.
 4. A process for fabricating a medicalassembly having a medical device at least a portion of which is formedof inorganic material, said medical assembly suitable for substantiallylong-term implantation in a host animal, said process comprising:modifying a surface of the medical device with plasma to form ahydrophilic adhesion-promoting surface; coating said hydrophilicadhesion-promoting surface with an alginate solution comprisingalginate; and reacting the alginate with alkaline earth metal cationsoxidizing said medical device prior to said modifying.
 5. The process ofclaim 1, said modifying comprising applying to the medical device anadhesion-promoting material.
 6. The process of claim 5, saidadhesion-promoting material comprising N, N-diethylaminotrimethylsilane.7. The process of claim 5, said adhesion-promoting material comprisingpolyvinyl pyrrolidone.
 8. The process of claim 2, said modifyingcomprising subjecting said biocompatible material to plasma bombardment.9. The process of claim 1, said modifying comprising coating saidmedical device with a biocompatible polymer and subsequently subjectingsaid biocompatible polymer to plasma bombardment.
 10. The process ofclaim 2, said modifying comprising coating said medical device with anadditional biocompatible polymer and subsequently subjecting saidbiocompatible polymer to plasma bombardment.
 11. The process of claim 1,said coating comprising contacting said hydrophilic adhesion-promotingsurface with a sodium alginate solution.
 12. The process of claim 1,further comprising purifying said alginate solution before said coating.13. The process of claim 1, said reacting comprising contacting saidalginate with a gelling solution comprising said alkaline earth metalcations.
 14. The process of claim 13, said gelling solution comprisingat least one of calcium, barium and zinc ions.
 15. The process of claim1, said reacting comprising contacting said alginate with a gellingsolution comprised of calcium chloride and then contacting said alginatewith a gelling solution of barium chloride.